Department of Cardiology, Dongzhimen Hospital, 248912Beijing University of Chinese Medicine, Beijing, China.
Department of Cardiology, Anzhen Hospital, Capital Medical University, Beijing, China.
Hum Exp Toxicol. 2022 Jan-Dec;41:9603271221124099. doi: 10.1177/09603271221124099.
In the present study, we aimed to investigate the role and mechanism of Parkinson's disease protein 7 (Park7) in myocardial infarction (MI). The Park7 expression in the serum and tissues was down-regulated in mice with MI. Recombinant Park7 protein protected against MI-induced injury and reduced oxidative stress in mice model. Conversely, knockout Park7 increased injury of MI and promoted oxidative stress in MI mice model. In embryonic rat cardiac myoblasts H9c2 cells, over-expression of Park7 reduced reactive oxygen species (ROS)-induced oxidative stress, while down-regulation of Park7 increased ROS-induced oxidative stress. Park7 combined nicotinamide adenine dinucleotide phosphate (NADPH) oxidase cytoplasmic subunit p47phox protein had direct effect on inducing NADPH activator. The inhibition of p47phox reduced the effects of Park7 in ROS production of HO-treated H9c2 cells. The regulation of NADPH participated in the effects of Park7 on ROS production of in both MI mice model and HO-treated H9c2 cells. Our data demonstrated that Park7 protects against oxidative stress in MI model direct through p47phox and NADPH oxidase 4.
在本研究中，我们旨在探讨帕金森病蛋白 7（Park7）在心肌梗死（MI）中的作用和机制。MI 小鼠血清和组织中的 Park7 表达下调。重组 Park7 蛋白可预防 MI 诱导的损伤并减轻 MI 小鼠模型中的氧化应激。相反，Park7 敲除增加了 MI 损伤并促进了 MI 小鼠模型中的氧化应激。在胚胎大鼠心肌细胞 H9c2 细胞中，Park7 的过表达可减轻活性氧（ROS）诱导的氧化应激，而下调 Park7 则增加了 ROS 诱导的氧化应激。Park7 与烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶胞质亚基 p47phox 蛋白直接结合，可诱导 NADPH 激活剂。p47phox 的抑制作用降低了 HO 处理的 H9c2 细胞中 Park7 对 ROS 产生的影响。NADPH 的调节参与了 Park7 在 MI 小鼠模型和 HO 处理的 H9c2 细胞中 ROS 产生中的作用。我们的数据表明，Park7 通过 p47phox 和 NADPH 氧化酶 4 直接保护 MI 模型免受氧化应激。
